Conductive cell Imprinted Polymers for Mature Induced Pluripotent Stem Cell Derived Cardiomyocytes
Description: Myocardial infarction related deaths have been abated over the past few decades in older populations in western countries while at the same time almost doubling in those under 50 years old. The coming epidemic will require new sources of donor organs due to the current and long standing shortage of organs and the well-known lack of adult cardiac regenerative capacity. Tissue engineering (TE) is a strategy which has emerged over the past 30 years to replace damaged tissues and is only recently coming into a viable stage of its evolution. The discovery of induced pluripotent stem cells was a major leap forward in engineering a patient specific cell source which can be expanded and reliably differentiate into cardiomyocytes for TE of cardiac tissue. However, like the early days of TE the new iPSC technology has been plagued with unforeseen issues such as lack of reproducibility between cell lines, batch to batch variation in differentiated products, immature phenotype of CM which can form teratoma, or cause arrhythmia in a patient. Though various biochemical cocktails and biomaterial strategies have been proposed to improve iPSC maturity to iCM, no universally accepted engineering standards have been developed or adopted to date. In this proposal, we suggest the use of 'cell-imprinted' (CI) conductive nanomaterial based scaffolds which can support iPSCs differentiation and maturation to iCM by creating nanoscale interfaces orders of magnitude lower impedance than traditional TE scaffolds, creating short-circuits between CM, and providing cues to enhance CM signaling and maturity. Aim 1: We will develop carbon nanotube (CNT) based CI polymer composites. CNT fillers and CI multiscale topography will enhance and synchronize iCM maturation and contractility. Aim 2: In this aim we will develop CI silver nanoparticles (AgNP) based conductive composites for iPSC differentiation. AgNP have distinct characteristics of antibacterial and anti-inflammatory properties. Aim 3: Electrical pacing of CM produced on CNT/Ag nanocomposite scaffolds for maturation. CNT/Ag based scaffolds have been used previously for enhancing the mature phenotype of CM from various sources with low likely hood of clinical viability but not CI conductive scaffold for guiding patient specific iPSCs first to a primitive-streak lineage followed by cardiac mesoderm and mature cardiomyocytes, using multiscale cell-imprinting technology, which if achieved is currently the holy grail of cardiac TE.
Funder: American Heart Association
Amount: $104,100
Funding type: fellowship
Funder scheme: Postdoctoral Fellowship
Start date: 2019-01-01
End date: 2019-04-08
Investigators: Michael Hill, Michael Hill
Institution: Michigan Technological University
Funded outputs count: 0
Funder award ID: 19POST34450219
OpenAlex ID: G7663888313